Cyclooxygenase, p38 Mitogen-Activated Protein Kinase (MAPK), Extracellular Signal-Regulated Kinase MAPK, Rho Kinase, and Src Mediate Hydrogen Peroxide-Induced Contraction of Rat Thoracic Aorta and Vena Cava

In hypertension, blood vessels exhibit increased reactive oxy-gen species production that may alter vascular tone. We pre-viously observed that H2O2 contracted rat thoracic vena cava under resting tone and aorta contracted with KCl. In arteries but not veins, H2O2-induced contraction required extracellular Ca2 influx. Because of this difference in Ca2 utilization, we hypothesized that signaling pathways mediating H2O2-induced contraction in vena cava under resting tone differed from those mediating H2O2-induced contraction in aorta contracted with KCl. Inhibitors of cyclooxygenase (COX) 1 and 2 (indomethacin, 10 M), thromboxane A2 (TXA2) receptors [ICI185282 (2RS,4RS,5SR-4-o-hydroxyphenyl-2-trifluoromethyl-1,3-diox-an-5-yl heptenoic acid), 10 M], p38 mitogen-activated protein kinase (MAPK) [SB203580 (4-[5-(4-fluorophenyl)-2-[4-(methyl-sulfonyl)phenyl]-1H-imidazol-4-yl]pyridine), 10 M], extracellu-lar signal-regulated kinase (Erk) [PD98059 (2-amino-3-me-thoxyflavone), 10 M], src [PP1 (4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine, 10 M], and rho kinase [Y27632 (trans-4-[(1R)-1-aminoethyl]-N-4-pyridinylcyclohex-anecarboxamide dihydrochloride), 10 M], significantly re-duced H2O2-induced contraction in vena cava under resting tone and aorta after KCl (30 mM) contraction. In contrast, the phosphatidylinositol 3-kinase (PI3-K) inhibitor LY294002 [2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one, 20 M] did not reduce aortic or venous H2O2-induced contraction. p3